This proposal is designed to study the biologic mechanisms involved in normal and abnormal development of craniofacial sutures. The methods to be used include cleared alizarin preparations, specimen radiography, light, electron and immunofluorescent microscopy and biochemical analyses for fibronectin, proteoglycans, and the different types of collagen in the sutural ligaments. The material to be studied consists of a collection of timed prenatal Macaca nemestrina specimens, normal and abnormal genetic strains of mice (wild type C57B1/6J, brachiomorphic bm/bm, and viable brindled MOvbr), rats and rabbits. The specific aims are: (1) to study histologic ultrastructural and biochemical differentiation of normal and genetically abnormal sutures in vivo, (2) to develop an in vitro system that will allow the application of stretching and compressive forces to developing sutures in tissue culture, and (3) to produce immature sutures in young calvariectomized rabbits for experiments on premature sutural fusion. The hypothesis to be tested is that sutural synostosis can be caused by intrauterine compression of immature cranial sutures in contrast to the sutural remodeling that results when mature sutures are compressed postnatally. If this clinical hypothesis is confirmed experimentally, it will provide a pathogenetic mechanism for this presently unexplained anomaly.